Open AccessThe core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability
Author(s) -
Sarah R. Hanson,
Elizabeth K. Culyba,
Tsui-Ling Hsu,
ChiHuey Wong,
Jeffery W. Kelly,
Evan T. Powers
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0810318105
Subject(s) - glycan , folding (dsp implementation) , protein folding , chemistry , folding funnel , energy landscape , biophysics , contact order , glycoprotein , kinetics , glycosylation , phi value analysis , biochemistry , downhill folding , biology , physics , electrical engineering , quantum mechanics , engineering
The folding energetics of the mono-N-glycosylated adhesion domain of the human immune cell receptor cluster of differentiation 2 (hCD2ad) were studied systematically to understand the influence of the N-glycan on the folding energy landscape. Fully elaborated N-glycan structures accelerate folding by 4-fold and stabilize the β-sandwich structure by 3.1 kcal/mol, relative to the nonglycosylated protein. The N-glycan's first saccharide unit accounts for the entire acceleration of folding and for 2/3 of the native state stabilization. The remaining third of the stabilization is derived from the next 2 saccharide units. Thus, the conserved N-linked triose core, ManGlcNAc2 , improves both the kinetics and the thermodynamics of protein folding. The native state stabilization and decreased activation barrier for folding conferred by N-glycosylation provide a powerful and potentially general mechanism for enhancing folding in the secretory pathway.